Juan Martin Hernandez will miss the historic fixture in Mendoza after he had to withdraw with a groin injury suffered at training yesterday.
The talismanic fly-half struggled with injuries for the last three years and his presence was always going to be key for the Pumas success.
He will be replaced by Nicolas Sanchez in the starting XV while Martin Rodríguez comes in for Lucas González Amorosino at full-back in the other change to the starting line up.
The Pumas have made history last week by taking part in their first ever Rugby Championship match but the whole country his now bracing itself to host the rematch against South Africa.
Argentina came up short last week and suffered a 27-6 defeat in Cape Town but with the crowd behind them, they could create the first upset of the competition.
The last time the two teams met in Argentina was in November 2005 and the Springboks had to fight until the end to secure a 34-23 win in Buenos Aires.
Adriaan Strauss replaces the injured Bismark du Plessis at hooker for the Springboks and Jacques Pogieter Pogieter comes in from the bench at blindside with Willem Alberts moving to No.8 and Keegan Daniel being retrograded to the bench
Winger Bryan Habana went through a late fitness test earlier in the week on his left ankle but was declared fit.
Argentina: Martín Rodríguez; Gonzalo Camacho, Marcelo Bosch, Santiago Fernández, Horacio Agulla; Nicolas Sanchez, Nicolás Vergallo; Rodrigo Roncero, Eusebio Guiñazú, Juan Figallo; Manuel Carizza, Patricio Albacete; Julio Farías Cabello, Álvaro Galindo, Juan Martín Fernández Lobbe.
Replacements (from): Marcos Ayerza, Martin Bustos Moyano, Lucas Gonzalez Amorosino, Juan Imhoff, Martin Landajo, Tomas Leonardi, Juan Pablo Orlandi, Bruno Postiglioni, Nicolas Sanchez, Leonardo Senatore, Tomas Vallejos
South Africa: Zane Kirchner; Bryan Habana, Jean de Villiers, Frans Steyn, Lwazi Mvovo; Morne Steyn, Francois Hougaard ; Tendai Mtawarira, Adriaan Strauss, Jannie du Plessis; Eben Etzebeth, Andries Bekker; Marcell Coetzee, Jacques Pogieter, Willem Alberts.
Replacements: Tian Liebenberg, Pat Cilliers, Flip van der Merwe, Keegan Daniel, Ruan Pienaar, Pat Lambie, JJ Engelbrecht.
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